RT Journal Article
SR Electronic
T1 Increased degradation of tryptophan in blood of patients with rheumatoid arthritis.
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 1935
OP 1939
VO 30
IS 9
A1 Katharina Schroecksnadel
A1 Sabine Kaser
A1 Maximilian Ledochowski
A1 Gabriele Neurauter
A1 Erich Mur
A1 Manfred Herold
A1 Dietmar Fuchs
YR 2003
UL http://www.jrheum.org/content/30/9/1935.abstract
AB OBJECTIVE: Activation of the enzyme indoleamine-(2,3)-dioxygenase (IDO) by interferon (IFN)-g leads to enhanced tryptophan conversion to kynurenine. In consequence of chronic immune activation, tryptophan availability is reduced, leading to inhibition of cell proliferation as protein synthesis is affected. Tryptophan deprivation due to IDO activation could therefore be effective in abrogating processes with high metabolic turnover, thus modulating cellular immune response. METHODS: Concentrations of tryptophan, kynurenine, and neopterin were measured by HPLC in the sera of 38 patients with rheumatoid arthritis (RA). The kynurenine:tryptophan ratios (kyn/trp) were calculated to estimate IDO activity. RESULTS: Tryptophan concentrations were lower in patients with RA (median, interquartile range: 44.95 microM, 40.31-49.95 microM) compared to healthy blood donors (62.62 microM, 57.27-74.61 microM; p < 0.001). Kynurenine in patients (1.86 microM, 1.54-2.31 microM) did not differ from controls (2.06 microM, 1.58-2.65 microM; NS). The kyn/trp ratio was higher in patients (42.39 mM/M, 37.02-48.60 mM/M) than in controls (31.72 mM/M; 27.95-35.03 mM/M; p < 0.001). Kynurenine concentrations (rs = 0.611; p < 0.001) and kyn/trp ratios (rs = 0.621; p < 0.001) correlated with neopterin concentrations, which indicate stimulated cellular immune response in patients with RA. CONCLUSIONS: The data point to a role of immune activation and Th1-type cytokine INF-g to induce elevated tryptophan degradation in patients with RA.